The majority of peptide and protein drugs are still administered by daily injections, thus being associated with compliance problems, pain-associated problems and major inconveniences to the patients. Hence, either prolonged injectable delivery systems or non-invasive delivery systems for such drugs are required.
The oral route offers the advantage of self-administration with high patient acceptance and compliance.
Oral and injectable prolonged release delivery of peptides and proteins remains challenging and continues to be the most attractive alternatives to the parenteral conventional delivery requiring daily administration. Despite intensive efforts invested over the last two decades no viable solution for oral delivery of hydrophilic potent macromolecules has emerged because of several drawbacks and hurdles associated with the poor intestinal membrane permeability of these hydrophilic macromolecules, limited oral bioavailability, instability in the gut and extensive rapid metabolism.
For the purpose of developing oral protein delivery systems with marked bioavailability, three approaches may be adopted:
(a) modification of the physicochemical properties of macromolecules;
(b) new functionalization of macromolecules; or
(c) use of improved cargo delivery via nanocarriers.
Nevertheless, it is essential, irrespective of the approach to maintain the initial biological activity of the proteins. An oral delivery system will need to enhance the intestinal membrane permeability of such macromolecules significantly to have a chance to be considered of potential for further clinical testing. A number of nano- and microparticulate delivery systems have been used to improve the oral absorption of the hydrophilic macromolecules and exhibited promising results, but are still suffering from limitations in term of intestinal absorption and drug stability protection.
Nano-sized systems (e.g., liposomes, lipid and polymeric nanoparticles, micelles, etc.) have been found to be advantageous over traditional formulations for protein delivery. Biotech drugs are predicted to become the main source of therapeutics in the near future [1]. Nevertheless, the therapeutic exploitation of such molecules relies on the possibility to develop suitable formulations that can satisfactorily overcome the intrinsic limitations of their use; namely low oral bioavailability and biological and physicochemical instability. However, oral administration of protein drugs encountered many difficulties due to their proteolytic instabilities and limited abilities to traverse biological barriers. Liposomes and micelles based delivery systems are not stable in the gut lumen and cannot elicit the adequate protection to the sensitive macromolecules.
Therefore, among the pharmaceutical formulations, nanoparticles have been successfully explored for drug delivery of peptidic drugs [2-4]. Nanoparticles, more specifically the biodegradable polymeric nanoparticles, possess excellent tissue biocompatibility, biodegradability, composition flexibility and small size, making them suitable for a variety of applications. Furthermore, these formulations were shown to enhance the drug bioavailability following oral administration [5].
Although encapsulation with biodegradable polymers is very attractive, the manufacturing processes are still complicated and expensive for hydrophilic macromolecules. In case of efficient entrapment approaches of protein drugs into these systems, encapsulation using polymers may provide (a) protection to the proteins from degradation during storage and delivery and (b) a sustained release profile when desired [6-8].